Search results for: smooth baseline hazard
Commenced in January 2007
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Edition: International
Paper Count: 2046

Search results for: smooth baseline hazard

1626 Comparison of Feedforward Back Propagation and Self-Organizing Map for Prediction of Crop Water Stress Index of Rice

Authors: Aschalew Cherie Workneh, K. S. Hari Prasad, Chandra Shekhar Prasad Ojha

Abstract:

Due to the increase in water scarcity, the crop water stress index (CWSI) is receiving significant attention these days, especially in arid and semiarid regions, for quantifying water stress and effective irrigation scheduling. Nowadays, machine learning techniques such as neural networks are being widely used to determine CWSI. In the present study, the performance of two artificial neural networks, namely, Self-Organizing Maps (SOM) and Feed Forward-Back Propagation Artificial Neural Networks (FF-BP-ANN), are compared while determining the CWSI of rice crop. Irrigation field experiments with varying degrees of irrigation were conducted at the irrigation field laboratory of the Indian Institute of Technology, Roorkee, during the growing season of the rice crop. The CWSI of rice was computed empirically by measuring key meteorological variables (relative humidity, air temperature, wind speed, and canopy temperature) and crop parameters (crop height and root depth). The empirically computed CWSI was compared with SOM and FF-BP-ANN predicted CWSI. The upper and lower CWSI baselines are computed using multiple regression analysis. The regression analysis showed that the lower CWSI baseline for rice is a function of crop height (h), air vapor pressure deficit (AVPD), and wind speed (u), whereas the upper CWSI baseline is a function of crop height (h) and wind speed (u). The performance of SOM and FF-BP-ANN were compared by computing Nash-Sutcliffe efficiency (NSE), index of agreement (d), root mean squared error (RMSE), and coefficient of correlation (R²). It is found that FF-BP-ANN performs better than SOM while predicting the CWSI of rice crops.

Keywords: artificial neural networks; crop water stress index; canopy temperature, prediction capability

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1625 The Effectiveness of Using Dramatic Conventions as the Teaching Strategy on Self-Efficacy for Children With Autism Spectrum Disorder

Authors: Tso Sheng-Yang, Wang Tien-Ni

Abstract:

Introduction and Purpose: Previous researchers have documented children with ASD (Autism Spectrum Disorders) prefer to escaping internal privates and external privates when they face tough conditions they can’t control or they don’t like.Especially, when children with ASD need to learn challenging tasks, such us Chinese language, their inappropriate behaviors will occur apparently. Recently, researchers apply positive behavior support strategies for children with ASD to enhance their self-efficacy and therefore to reduce their adverse behaviors. Thus, the purpose of this research was to design a series of lecture based on art therapy and to evaluate its effectiveness on the child’s self-efficacy. Method: This research was the single-case design study that recruited a high school boy with ASD. Whole research can be separated into three conditions. First, baseline condition, before the class started and ended, the researcher collected participant’s competencies of self-efficacy every session. In intervention condition, the research used dramatic conventions to teach the child in Chinese language twice a week.When the data was stable across three documents, the period entered to the maintenance condition. In maintenance condition, the researcher only collected the score of self-efficacynot to do other interventions five times a month to represent the effectiveness of maintenance.The time and frequency of data collection among three conditions are identical. Concerning art therapy, the common approach, e.g., music, drama, or painting is to use art medium as independent variable. Due to visual cues of art medium, the ASD can be easily to gain joint attention with teachers. Besides, the ASD have difficulties in understanding abstract objectives Thus, using the drama convention is helpful for the ASD to construct the environment and understand the context of Classical Chinese. By real operation, it can improve the ASD to understand the context and construct prior knowledge. Result: Bassd on the 10-points Likert scale and research, we product following results. (a) In baseline condition, the average score of self-efficacyis 1.12 points, rangedfrom 1 to 2 points, and the level change is 0 point. (b)In intervention condition, the average score of self-efficacy is 7.66 points rangedfrom 7 to 9 points, and the level change is 1 point. (c)In maintenance condition, the average score of self-efficacy is 6.66 points rangedfrom 6 to 7 points, and the level change is 1 point. Concerning immediacy of change, between baseline and intervention conditions, the difference is 5 points. No overlaps were found between these two conditions. Conclusion: According to the result, we find that it is effective that using dramatic conventions a s teaching strategies to teach children with ASD. The result presents the score of self-efficacyimmediately enhances when the dramatic conventions commences. Thus, we suggest the teacher can use this approach and adjust, based on the student’s trait, to teach the ASD on difficult task.

Keywords: dramatic conventions, autism spectrum disorder, slef-efficacy, teaching strategy

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1624 Superconvergence of the Iterated Discrete Legendre Galerkin Method for Fredholm-Hammerstein Equations

Authors: Payel Das, Gnaneshwar Nelakanti

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In this paper we analyse the iterated discrete Legendre Galerkin method for Fredholm-Hammerstein integral equations with smooth kernel. Using sufficiently accurate numerical quadrature rule, we obtain superconvergence rates for the iterated discrete Legendre Galerkin solutions in both infinity and $L^2$-norm. Numerical examples are given to illustrate the theoretical results.

Keywords: hammerstein integral equations, spectral method, discrete galerkin, numerical quadrature, superconvergence

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1623 Incorporation of Safety into Design by Safety Cube

Authors: Mohammad Rajabalinejad

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Safety is often seen as a requirement or a performance indicator through the design process, and this does not always result in optimally safe products or systems. This paper suggests integrating the best safety practices with the design process to enrich the exploration experience for designers and add extra values for customers. For this purpose, the commonly practiced safety standards and design methods have been reviewed and their common blocks have been merged forming Safety Cube. Safety Cube combines common blocks for design, hazard identification, risk assessment and risk reduction through an integral approach. An example application presents the use of Safety Cube for design of machinery.

Keywords: safety, safety cube, product, system, machinery, design

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1622 Variation of Litter Chemistry under Intensified Drought: Consequences on Flammability

Authors: E. Ormeno, C. Gutigny, J. Ruffault, J. Madrigal, M. Guijarro, C. Lecareux, C. Ballini

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Mediterranean plant species feature numerous metabolic and morpho-physiological responses crucial to survive under both, typical Mediterranean drought conditions and future aggravated drought expected by climate change. Whether these adaptive responses will, in turn, increase the ecosystem perturbation in terms of fire hazard, is an issue that needs to be addressed. The aim of this study was to test whether recurrent and aggravated drought in the Mediterranean area favors the accumulation of waxes in leaf litter, with an eventual increase of litter flammability. The study was conducted in 2017 in a garrigue in Southern France dominated by Quercus coccifera, where two drought treatments were used: a treatment with recurrent aggravated drought consisting of ten rain exclusion structures which withdraw part of the annual precipitation since January 2012, and a natural drought treatment where Q. coccifera stands are free of such structures and thus grow under natural precipitation. Waxes were extracted with organic solvent and analyzed by GC-MS and litter flammability was assessed through measurements of the ignition delay, flame residence time and flame intensity (flame height) using an epiradiator as well as the heat of combustion using an oxygen bomb calorimeter. Results show that after 5 years of rain restriction, wax content in the cuticle of leaf litter increases significantly compared to shrubs growing under natural precipitation, in accordance with the theoretical knowledge which expects increases of cuticle waxes in green leaves in order to limit water evapotranspiration. Wax concentrations were also linearly and positively correlated to litter flammability, a correlation that lies on the high flammability own to the long-chain alkanes (C25-C31) found in leaf litter waxes. This innovative investigation shows that climate change is likely to favor ecosystem fire hazard through accumulation of highly flammable waxes in litter. It also adds valuable information about the types of metabolites that are associated with increasing litter flammability, since so far, within the leaf metabolic profile, only terpene-like compounds had been related to plant flammability.

Keywords: cuticular waxes, drought, flammability, litter

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1621 Enhancement of Aircraft Longitudinal Stability Using Tubercles

Authors: Muhammad Umer, Aishwariya Giri, Umaiyma Rakha

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Mimicked from the humpback whale flippers, the application of tubercle technology is seen to be particularly advantageous at high angles of attack. This particular advantage is of paramount importance when it comes to structures producing lift at high angles of attack. This characteristic of the technology makes it ideal for horizontal stabilizers and selecting the same as the subject of study to identify and exploit the advantage highlighted by researchers on airfoils, this project aims in establishing a foundation for the application of the bio-mimicked technology on an existing aircraft. Using a baseline and 2 tubercle configuration integrated models, the project targets to achieve the twin aim of highlighting the possibility and merits over the base model and also choosing the right configuration in providing the best characteristic suitable for high angles of attack. To facilitate this study, the required models are generated using Solidworks followed by trials in a virtual aerodynamic environment using Fluent in Ansys for resolving the project objectives. Following a structured plan, the aim is to initially identify the advantages mathematically and then selecting the optimal configuration, simulate the end configuration at angles mimicking the actual operation envelope for the particular structure. Upon simulating the baseline configuration at various angles of attack, the stall angle was determined to be 22 degrees. Thus, the tubercle configurations will be simulated and compared at 4 different angles of attacks: 0, 10, 20, and 24. Further, after providing the optimum configuration of horizontal stabilizers, this study aims at the integration of aircraft structure so that the results better imply the end deliverables of real life application. This draws the project scope closer at this point into longitudinal static stability considerations and improvements in the manoeuvrability characteristics. The objective of the study is to achieve a complete overview ready for real life application with marked benefits obtainable from bio morphing of the tubercle technology.

Keywords: flow simulation, horizontal stabilizer, stability enhancement, tubercle

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1620 Comparing the Efficacy of Minimally Supervised Home-Based and Closely Supervised Gym Based Exercise Programs on Weight Reduction and Insulin Resistance after Bariatric Surgery

Authors: Haleh Dadgostar, Sara Kaviani, Hanieh Adib, Ali Mazaherinezhad, Masoud Solaymani-Dodaran, Fahimeh Soheilipour, Abdolreza Pazouki

Abstract:

Background and Objectives: Effectiveness of various exercise protocols in weight reduction after bariatric surgery has not been sufficiently explored in the literature. We compared the effect of minimally supervised home-based and closely supervised Gym based exercise programs on weight reduction and insulin resistance after bariatric surgery. Methods: Women undergoing gastric bypass surgery were invited to participate in an exercise program and were randomly allocated into two groups. They were either offered a minimally supervised home-based (MSHB) or closely supervised Gym-based (CSGB) exercise program. The CSGB protocol constitute two sessions per week of training under ACSM guidelines. In the MSHB protocol participants received a notebook containing a list of recommended aerobic and resistance exercises, a log to record their activity and a schedule of follow up phone calls and clinic visits. Both groups received a pedometer. We measured their weight, BMI, lipid profile, FBS, and insulin level at the baseline and after 20 weeks of exercise and were compared at the end of the study. Results: A total of 80 patients completed our study (MSHB=38 and CSGB=42). The baseline comparison showed that the two groups are similar. Using the ANCOVA method of analysis the mean change in BMI (covariate: BMI at the beginning of the study) was slightly better in CSGB compared with the MSHB (between-group mean difference: 3.33 (95%CI 4.718 to 1.943, F: 22.844 p < 0.001)). Conclusion: Our results showed that both MSHB and CSGB exercise methods are somewhat equally effective in improvement of studied factors in the two groups. With considerably lower costs of Minimally Supervised Home Based exercise programs, these methods should be considered when adequate funding are not available.

Keywords: postoperative exercise, insulin resistance, bariatric surgery, morbid obesity

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1619 A New Distribution and Application on the Lifetime Data

Authors: Gamze Ozel, Selen Cakmakyapan

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We introduce a new model called the Marshall-Olkin Rayleigh distribution which extends the Rayleigh distribution using Marshall-Olkin transformation and has increasing and decreasing shapes for the hazard rate function. Various structural properties of the new distribution are derived including explicit expressions for the moments, generating and quantile function, some entropy measures, and order statistics are presented. The model parameters are estimated by the method of maximum likelihood and the observed information matrix is determined. The potentiality of the new model is illustrated by means of real life data set.

Keywords: Marshall-Olkin distribution, Rayleigh distribution, estimation, maximum likelihood

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1618 Developing a Process and Cost Model for Xanthan Biosynthesis from Bioethanol Production Waste Effluents

Authors: Bojana Ž. Bajić, Damjan G. Vučurović, Siniša N. Dodić, Jovana A. Grahovac, Jelena M. Dodić

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Biosynthesis of xanthan, a microbial polysaccharide produced by Xanthomonas campestris, is characterized by the possibility of using non-specific carbohydrate substrates, which means different waste effluents can be used as a basis for the production media. Potential raw material sources for xanthan production come from industries with large amounts of waste effluents that are rich in compounds necessary for microorganism growth and multiplication. Taking into account the amount of waste effluents generated by the bioethanol industry and the fact that it contains a high inorganic and organic load it is clear that they represent a potential environmental pollutants if not properly treated. For this reason, it is necessary to develop new technologies which use wastes and wastewaters of one industry as raw materials for another industry. The result is not only a new product, but also reduction of pollution and environmental protection. Biotechnological production of xanthan, which consists of using biocatalysts to convert the bioethanol waste effluents into a high-value product, presents a possibility for sustainable development. This research uses scientific software developed for the modeling of biotechnological processes in order to design a xanthan production plant from bioethanol production waste effluents as raw material. The model was developed using SuperPro Designer® by using input data such as the composition of raw materials and products, defining unit operations, utility consumptions, etc., while obtaining capital and operating costs and the revenues from products to create a baseline production plant model. Results from this baseline model can help in the development of novel biopolymer production technologies. Additionally, a detailed economic analysis showed that this process for converting waste effluents into a high value product is economically viable. Therefore, the proposed model represents a useful tool for scaling up the process from the laboratory or pilot plant to a working industrial scale plant.

Keywords: biotechnology, process model, xanthan, waste effluents

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1617 Diversity and Ecological Analysis of Vascular Epiphytes in Gera Wild Coffee Forest, Jimma Zone of Oromia Regional State, Ethiopia

Authors: Bedilu Tafesse

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The diversity and ecological analysis of vascular epiphytes was studied in Gera Forest in southwestern Ethiopia at altitudes between 1600 and 2400 m.a.s.l. A total area of 4.5 ha was surveyed in coffee and non-coffee forest vegetation. Fifty sampling plots, each 30 m x 30 m (900 m2), were used for the purpose of data collection. A total of 59 species of vascular epiphytes were recorded, of which 34 (59%) were holo epiphytes, two (4%) were hemi epiphytes and 22 (37%) species were accidental vascular epiphytes. To study the altitudinal distribution of vascular epiphytes, altitudes were classified into higher >2000, middle 1800-2000 and lower 1600-1800 m.a.s.l. According to Shannon-Wiener Index (H/= 3.411) of alpha diversity the epiphyte community in the study area is medium. There was a statistically significant difference between host bark type and epiphyte richness as determined by one-way ANOVA p = 0.001 < 0.05. The post-hoc test shows that there is significant difference of vascular epiphytes richness between smooth bark with rough, flack and corky bark (P =0.001< 0.05), as well as rough and cork bark (p =0.43 <0.05). However, between rough and flack bark (p = 0.753 > 0.05) and between flack and corky bark (p = 0.854 > 0.05) no significant difference of epiphyte abundance was observed. Rough bark had 38%, corky 26%, flack 25%, and only 11% vascular epiphytes abundance occurred on smooth bark. The regression correlation test, (R2 = 0.773, p = 0.0001 < 0.05), showed that the number of species of vascular epiphytes and host DBH size are positively correlated. The regression correlation test (R2 = 0.28, p = 0.0001 < 0.05), showed that the number of species and host tree height positively correlated. The host tree preference of vascular epiphytes was recorded for only Vittaria volkensii species hosted on Syzygium guineense trees. The result of similarity analysis indicated that Gera Forest showed the highest vascular epiphytic similarity (0.35) with Yayu Forest and shared the least vascular epiphytic similarity (0.295) with Harenna Forest. It was concluded that horizontal stems and branches, large and rough, flack and corky bark type trees are more suitable for vascular epiphytes seedling attachments and growth. Conservation and protection of these phorophytes are important for the survival of vascular epiphytes and increase their ecological importance.

Keywords: accidental epiphytes, hemiepiphyte, holoepiphyte, phorophyte

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1616 Fast Terminal Sliding Mode Controller For Quadrotor UAV

Authors: Vahid Tabrizi, Reza GHasemi, Ahmadreza Vali

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This paper presents robust nonlinear control law for a quadrotor UAV using fast terminal sliding mode control. Fast terminal sliding mode idea is used for introducing a nonlinear sliding variable that guarantees the finite time convergence in sliding phase. Then, in reaching phase for removing chattering and producing smooth control signal, continuous approximation idea is used. Simulation results show that the proposed algorithm is robust against parameter uncertainty and has better performance than conventional sliding mode for controlling a quadrotor UAV.

Keywords: quadrotor UAV, fast terminal sliding mode, second order sliding mode t

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1615 A Randomised Controlled Trial on the Nurse-Led Smartphone-Based Self-Management Programme for Type 2 Diabetes Patients with Poor Glycemic Control

Authors: Wenru Wang

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Over the past decades, Asia has emerged as the ‘diabetes epicentre’ in the world due to rapid economic development, urbanization and nutrition transition. There is an urgent need to develop more effective and cost-effective care management strategies in response to this rising diabetes epidemic. This study aims to develop and compare a nurse-led smartphone-based self-management programme with an existing nurse-led diabetes service on health-related outcomes among type 2 diabetes patients with poor glycemic control in Singapore. We proposed a randomized controlled trial with pre- and repeated post-tests control group design. A total of 128 type 2 diabetes patients with poor glycemic control will be recruited from the diabetes clinic of an acute public hospital in Singapore through convenience sampling. Study participants will be either randomly allocated to the experimental group or control group. Outcome measures used will include the 10-item General Self-Efficacy Scale, 11-item Revised Summary of Diabetes Self-care Activities, and 19-item Diabetes-Dependent Quality of Life. Data will be collected at 3-time points: baseline, three months and six months from the baseline, respectively. It is expected that this programme will be an alternative offered to diabetes patients to master their self-care management skills, in addition to the existing diabetes service provided in diabetes clinics in Singapore hospitals. Also, the self-supporting and less resource-intensive nature of this programme, through the use of smartphone app as a mode of intervention delivery, will greatly reduce nurses’ direct contact time with patients and allow more time to be allocated to those who require more attention. The study has been registered with clinicaltrials.gov. The trial registration number is NCT03088475.

Keywords: type 2 diabetes, poor glycaemic control, nurse-led, smartphone-based, self-management, health-relevant outcomes

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1614 Effects of Aerobic Dance on Systolic Blood Pressure in Stage 1 Hypertensive Individuals in Uganda

Authors: Loyce Nahwera, Joy Wachira, Edwin Kiptolo, Constance Nsibambi, Mshilla Maghanga, Timothy Makubuya

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Introduction: Hypertension is one of the most prominent risk factors for cardiovascular diseases globally, and it can be modified through lifestyle interventions such as exercise. The objective of this study was to investigate the effects of a 12-week aerobic dance programme on systolic blood pressure (SBP) in stage 1 hypertensive individuals. Methods: This study employed an experimental research design. A total of 36 stage 1 hypertensive individuals who were randomly assigned into experimental and control groups completed the study. Systolic BP was measured using a mercury sphygmomanometer at baseline, mid-point and after the program. The experimental group participants trained 3 days a week, 45 minutes per session, at a moderate intensity of 40-60% of maximum oxygen consumption (VO2max) monitored by Garmin heart rate monitors. Data were analyzed using SPSS version 20. The significance level was set at p<0.05. A paired sample t-test was used to compare mean differences within the groups. Results: Data from the 36 participants (22 males and 14 females) (experimental; n=18, control; n=18) show that the experimental group had a mean SBP of 143.83±6.382 mmHg at baseline while the control had a mean of 137.61±6.400 mmHg. Following the end of a 6-week aerobic dance, the mean SBP of the experimental group reduced to 138.06±9.539 mmHg while that of the control marginally decreased to 137.00±8.073 mmHg. At the completion of a 12-week program, the mean SBP of the experimental group reduced to 136.33±9.191 mmHg, while that of the control marginally increased to 139.56±9.954 mmHg. This implies that both the 6-week and 12-week aerobic dance program reduced the SBP of the experimental group by 5.77±7.133 mmHg and 7.50±8.487 mmHg, respectively, while the control group fast reduced marginally by 0.61 before ultimately increasing by 1.95±7.974 mmHg at 12-weeks. The changes were statistically significant (p<0.05) at both 6 and 12 weeks of an aerobic dance program. Conclusion: The study concluded that aerobic dance is an effective non-pharmacological method for managing SBP of stage 1 hypertensive individuals both in the short-term (6 weeks) and long-term (12 weeks).

Keywords: aerobic dance, blood pressure, stage 1 hypertension, systolic blood pressure.

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1613 Dorsal Root Ganglion Neuromodulation as an Alternative to Opioids in the Evolving Healthcare Crisis

Authors: Adam J. Carinci

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Background: The opioid epidemic is the most pressing healthcare crisis of our time. There is increasing recognition that opioids have limited long-term efficacy and are associated with hyperalgesia, addiction, and increased morbidity and mortality. Therefore, alternative strategies to combat chronic pain are paramount. We initiated a multicenter retrospective case series to review the efficacy of DRG stimulation in facilitating opioid tapering, opioid discontinuation and as a viable alternative to chronic opioid therapy. Purpose: The dorsal root ganglion (DRG) plays a key role in the development and maintenance of pain. Recent innovations in neuromodulation, specifically, dorsal root ganglion stimulation, offers an effective alternative to opioids in the treatment of chronic pain. This retrospective case series demonstrates preliminary evidence that DRG stimulation facilitates opioid tapering, opioid discontinuation and presents a viable alternative to chronic opioid therapy. Procedure: This small multicenter retrospective case series provides preliminary evidence that DRG stimulation facilitates opioid weaning, opioid tapering and is a viable option to opioid therapy in the treatment of chronic pain. A retrospective analysis was completed. Visual analog scale pain scores and pain medication usage were collected at the baseline visit and after four weeks, 3 months and 6 months of treatment. Ten consecutive patients across two study centers were included. The pain was rated 7.38 at baseline and decreased to 1.50 at the 4-week follow-up, a reduction of 79.5%. All patients significantly decreased their opioid pain medication use with an average > 30% reduction in morphine equivalents and four were able to discontinue their medications entirely. Conclusion: This Retrospective case series demonstrates preliminary evidence that DRG stimulation facilitates opioid tapering, opioid discontinuation and presents a viable alternative to chronic opioid therapy.

Keywords: dorsal root ganglion, neuromodulation, opioid sparing, stimulation

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1612 Benefits of Whole-Body Vibration Training on Lower-Extremity Muscle Strength and Balance Control in Middle-Aged and Older Adults

Authors: Long-Shan Wu, Ming-Chen Ko, Chien-Chang Ho, Po-Fu Lee, Jenn-Woei Hsieh, Ching-Yu Tseng

Abstract:

This study aimed to determine the effects of whole-body vibration (WBV) training on lower-extremity muscle strength and balance control performance among community-dwelling middle-aged and older adults in the United States. Twenty-nine participants without any contraindication of performing WBV exercise completed all the study procedures. Participants were randomly assigned to do body weight exercise with either an individualized vibration frequency and amplitude, a fixed vibration frequency and amplitude, or no vibration. Isokinetic knee extensor power, limits of stability, and sit-to-stand tests were performed at the baseline and after 8 weeks of training. Neither the individualized frequency-amplitude WBV training protocol nor the fixed frequency-amplitude WBV training protocol improved isokinetic knee extensor power. The limits of stability endpoint excursion score for the individualized frequency-amplitude group increased by 8.8 (12.9%; p = 0.025) after training. No significant differences were observed in fixed and control group. The maximum excursion score for the individualized frequency-amplitude group at baseline increased by 9.2 (11.5%; p = 0.006) after training. The average weight transfer time score significantly decreased by 0.21 s in the fixed group. The participants in the individualized group showed a significant increase (3.2%) in weight rising index score after 8 weeks of WBV training. These results suggest that 8 weeks of WBV training improved limit of stability and sit-to-stand performance. Future studies need to determine whether WBV training improves other factors that can influence posture control.

Keywords: whole-body vibration training, muscle strength, balance control, middle-aged and older adults

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1611 Enhancing Seismic Resilience in Urban Environments

Authors: Beatriz González-rodrigo, Diego Hidalgo-leiva, Omar Flores, Claudia Germoso, Maribel Jiménez-martínez, Laura Navas-sánchez, Belén Orta, Nicola Tarque, Orlando Hernández- Rubio, Miguel Marchamalo, Juan Gregorio Rejas, Belén Benito-oterino

Abstract:

Cities facing seismic hazard necessitate detailed risk assessments for effective urban planning and vulnerability identification, ensuring the safety and sustainability of urban infrastructure. Comprehensive studies involving seismic hazard, vulnerability, and exposure evaluations are pivotal for estimating potential losses and guiding proactive measures against seismic events. However, broad-scale traditional risk studies limit consideration of specific local threats and identify vulnerable housing within a structural typology. Achieving precise results at neighbourhood levels demands higher resolution seismic hazard exposure, and vulnerability studies. This research aims to bolster sustainability and safety against seismic disasters in three Central American and Caribbean capitals. It integrates geospatial techniques and artificial intelligence into seismic risk studies, proposing cost-effective methods for exposure data collection and damage prediction. The methodology relies on prior seismic threat studies in pilot zones, utilizing existing exposure and vulnerability data in the region. Emphasizing detailed building attributes enables the consideration of behaviour modifiers affecting seismic response. The approach aims to generate detailed risk scenarios, facilitating prioritization of preventive actions pre-, during, and post-seismic events, enhancing decision-making certainty. Detailed risk scenarios necessitate substantial investment in fieldwork, training, research, and methodology development. Regional cooperation becomes crucial given similar seismic threats, urban planning, and construction systems among involved countries. The outcomes hold significance for emergency planning and national and regional construction regulations. The success of this methodology depends on cooperation, investment, and innovative approaches, offering insights and lessons applicable to regions facing moderate seismic threats with vulnerable constructions. Thus, this framework aims to fortify resilience in seismic-prone areas and serves as a reference for global urban planning and disaster management strategies. In conclusion, this research proposes a comprehensive framework for seismic risk assessment in high-risk urban areas, emphasizing detailed studies at finer resolutions for precise vulnerability evaluations. The approach integrates regional cooperation, geospatial technologies, and adaptive fragility curve adjustments to enhance risk assessment accuracy, guiding effective mitigation strategies and emergency management plans.

Keywords: assessment, behaviour modifiers, emergency management, mitigation strategies, resilience, vulnerability

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1610 Effect of Dietarty Diversity on Maternal Dietary Diversity of Anemia of the Mother during Pregnancy and Prenatal Outcomes: Prospective Cohort Study in Rural Central Ethiopia

Authors: Taddese Alemu Zerfu, Melaku Umeta Deressa, Kaleab Baye

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Background: Maternal and child under-nutrition is the underlying cause of 3•5 million annual deaths, globally. Anemia during pregnancy is among the leading nutritional disorders with serious short and long term consequences to both the mother and fetus. Objective: Examine the effect of dietary diversity on maternal anemia, nutritional status and key pregnancy outcomes of pregnancy. Methods: A prospective cohort study design, involving a total of 432 eligible pregnant women, in their second antenatal care visit was conducted between August 2014 to March, 2015. The individual dietary diversity status of mothers was used as the exposure variable to select, enroll and follow the mothers. All mothers were enrolled during second antenatal care visit and followed until delivery. Epi-data, SPSS and STATA software are used to enter and analyze the data. Chi-square test, independent 't'-test, and GLM are used to calculate risk, association and differences between key variables at P < 0.05. Results: Study participants did not differ in many of the basic characteristics (p < 0.05). The incidence of maternal anemia increased significantly from 28.6% to 32.1% between baseline and term. Pregnant mothers with inadequate dietary diversity groups had more (56% at baseline and 68% at term) risk of anemia than the comparison (adequate) groups, (RR, 1.56 and 1.68; 95% CI, 1.24 - 1.83 and 1.39 - 2.04). The overall incidence of still birth, low birth weight and pre-term birth was 4.5%, 9.1% and 13.6%, respectively. The variation of these outcomes was significant across study groups (P < 0.05). Conclusion and recommendations: Dietary diversity status of pregnant mothers has significant effect on the incidence of anemia and key pregnancy outcomes in resource limited settings, like rural Ethiopia. Therefore, apart from the ongoing routine IFA supplementation, special emphasis should be given to dietary diversity of mothers to improve related outcomes of pregnancy and maternal health.

Keywords: anemia, birth weight, dietary diversity, pregnancy, pregnancy outcome

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1609 The Effect of a Muscarinic Antagonist on the Lipase Activity

Authors: Zohreh Bayat, Dariush Minai-Tehrani

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Lipases constitute one of the most important groups of industrial enzymes that catalyze the hydrolysis of triacylglycerol to glycerol and fatty acids. Muscarinic antagonist relieves smooth muscle spasm of the gastrointestinal tract and effect on the cardiovascular system. In this research, the effect of a muscarinic antagonist on the lipase activity of Pseudomonas aeruginosa was studied. Lineweaver–Burk plot showed that the drug inhibited the enzyme by competitive inhibition. The IC50 value (60 uM) and Ki (30 uM) of the drug revealed the drug bound to the enzyme with high affinity. Determination of enzyme activity in various pH and temperature showed that the maximum activity of lipase was at pH 8 and 60°C both in presence and absence of the drug.

Keywords: bacteria, inhibition, kinetics, lipase

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1608 A Predator-Prey System with Singularity at the Origin

Authors: Nabil Beroual, Tewfik Sari

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We consider the Gause-type predator-prey system in the case where the response function is not smooth at the origin. We discuss the conditions under which this system has exactly one stable limit cycle or has a positive stable equilibrium point, and we describe the basin of attraction of the stable limit cycle and the stable equilibrium point, respectively. Our results correct previous results of the existing literature.

Keywords: predator-prey model, response function, singularity, basin of attraction, limit cycle

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1607 “Friction Surfaces” of Airport Emergency Plan

Authors: Jakub Kraus, Vladimír Plos, Peter Vittek

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This article focuses on the issue of airport emergency plans, which are documents describing reactions to events with impact on aviation safety or aviation security. The article specifically focuses on the use and creation of emergency plans, where could be found a number of disagreements between different stakeholders, for which the airport emergency plan applies. Those are the friction surfaces of interfaces, which is necessary to identify and ensure them smooth process to avoid dangerous situations or delay.

Keywords: airport emergency plan, aviation safety, aviation security, comprehensive management system, friction surfaces of airport emergency plan, interfaces of processes

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1606 Comparison of Cardiomyogenic Potential of Amniotic Fluid Mesenchymal Stromal Cells Derived from Normal and Isolated Congenital Heart Defective Fetuses

Authors: Manali Jain, Neeta Singh, Raunaq Fatima, Soniya Nityanand, Mandakini Pradhan, Chandra Prakash Chaturvedi

Abstract:

Isolated Congenital Heart Defect (ICHD) is the major cause of neonatal death worldwide among all forms of CHDs. A significant proportion of fetuses with ICHD die in the neonatal period if no treatment is provided. Recently, stem cell therapies have emerged as a potential approach to ameliorate ICHD in children. ICHD is characterized by cardiac structural abnormalities during embryogenesis due to alterations in the cardiomyogenic properties of a pool of cardiac progenitors/ stem cells associated with fetal heart development. The stem cells present in the amniotic fluid (AF) are of fetal origin and may reflect the physiological and pathological changes in the fetus during embryogenesis. Therefore, in the present study, the cardiomyogenic potential of AF-MSCs derived from fetuses with ICHD (ICHD AF-MSCs) has been evaluated and compared with that of AF-MSCs of structurally normal fetuses (normal AF-MSCs). Normal and ICHD AF-MSC were analyzed for the expression of cardiac progenitor markers viz., stage-specific embryonic antigen-1 (SSEA-1), vascular endothelial growth factor 2 (VEGFR-2) and platelet-derived growth factor receptor-alpha (PDGFR-α) by flow cytometry. The immunophenotypic characterization revealed that ICHD AF-MSCs have significantly lower expression of cardiac progenitor markers VEGFR-2 (0.14% ± 0.6 vs.48.80% ± 0.9; p <0.01), SSEA-1 (70.86% ± 2.4 vs. 88.36% ±2.7; p <0.01), and PDGFR-α (3.92% ± 1.8 vs. 47.59% ± 3.09; p <0.01) in comparison to normal AF-MSCs. Upon induction with 5’-azacytidine for 21 days, ICHD AF-MSCs showed a significantly down-regulated expression of cardiac transcription factors such as GATA-4 (0.4 ± 0.1 vs. 6.8 ± 1.2; p<0.01), ISL-1 (2.3± 0.6 vs. 14.3 ± 1.12; p<0.01), NK-x 2-5 (1.1 ± 0.3 vs. 14.1 ±2.8; p<0.01), TBX-5 (0.4 ± 0.07 vs. 4.4 ± 0.3; p<0.001), and TBX-18 (1.3 ± 0.2 vs. 4.19 ± 0.3; p<0.01) when compared with the normal AF-MSCs. Furthermore, immunocytochemical staining revealed that both types of AF-MSCs could differentiate into cardiovascular lineages and express cardiomyogenic, endothelial, and smooth muscle actin markers, viz., cardiac troponin (cTNT), CD31, and alpha-smooth muscle actin (α-SMA). However, normal AF-MSCs showed an enhanced expression of cTNT (p<0.001), CD31 (p<0.01), and α-SMA (p<0.05), compared to ICHD AF-MSCs. Overall, these results suggest that the ICHD-AF-MSCs have a defective cardiomyogenic differentiation potential and that the defects in these stem cells may have a role in the pathogenesis of ICHD.

Keywords: amniotic fluid, cardiomyogenic potential, isolated congenital heart defect, mesenchymal stem cells

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1605 The Impact of Nutrition Education Intervention in Improving the Nutritional Status of Sickle Cell Patients

Authors: Lindy Adoma Dampare, Marina Aferiba Tandoh

Abstract:

Sickle cell disease (SCD) is an inherited blood disorder that mostly affects individuals in sub-Saharan Africa. Nutritional deficiencies have been well established in SCD patients. In Ghana, studies have revealed the prevalence of malnutrition, especially amongst children with SCD and hence the need to develop an evidence-based comprehensive nutritional therapy for SCD to improve their nutritional status. The aim of the study was to develop and assess the effect of a nutrition education material on the nutritional status of SCD patients in Ghana. This was a pre-post interventional study. Patients between the ages of 2 to 60 years were recruited from the Tema General Hospital. Following a baseline nutrition knowledge (NK), beliefs, sanitary practice and dietary consumption pattern assessment, a twice-monthly nutrition education was carried out for 3 months, followed by a post-intervention assessment. Nutritional status of SCD patients was assessed using a 3-days dietary recall and anthropometric measurements. Nutrition education (NE) was given to SCD adults and caregivers of SCD children. Majority of the caregivers (69%) and SCD adult (82%) at baseline had low NK. The level of NK improved significantly in SCD adults (4.18±1.83 vs. 10.00±1.00, p<0.001) and caregivers (5.58 ± 2.25 vs.10.44± 0.846, p<0.001) after NE. Increase in NK improved dietary intake and dietary consumption pattern of SCD patients. Significant increase in weight (23.2±11.6 vs. 25.9±12.1, p=0.036) and height (118.5±21.9 vs. 123.5±22.2, p=0.011) was observed in SCD children at post intervention. Stunting (10.5% vs. 8.6%, p=0.62) and wasting (22.1% vs. 14.4%, p=0.30) reduced in SCD children after NE although not statistically significant. Reduction (18.2% vs. 9.1%) in underweight and an increase (18.2% vs. 27.3%) in overweight SCD adults was recorded at post intervention. Fat mass remained the same while high muscle mass increased (18.2% vs. 27.3%) at post intervention in SCD adult. Anaemic status of SCD patients improved at post intervention and the improvement was statistically significant amongst SCD children. Nutrition education improved the NK of SCD caregivers and adults hence, improving the dietary consumption pattern and nutrient intake of SCD patients. Overall, NE improved the nutritional status of SCD patients. This study shows the potential of nutrition education in improving the nutritional knowledge, dietary consumption pattern, dietary intake and nutritional status of SCD patients, and should be further explored.

Keywords: sickle cell disease, nutrition education, dietary intake, nutritional status

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1604 Preparedness for Nurses to Adopt the Implementation of Inpatient Medication Order Entry (IPMOE) System at United Christian Hospital (UCH) in Hong Kong

Authors: Yiu K. C. Jacky, Tang S. K. Eric, W. Y. Tsang, C. Y. Li, C. K. Leung

Abstract:

Objectives : (1) To enhance the competence of nurses on using IPMOE for drug administration; (2) To ensure the transition on implementation of IPMOE in safer and smooth way hospital-wide. Methodology: (1) Well-structured Governance: To make provision for IPMOE implementation, multidisciplinary governance structure at Corporate and Local levels are well established. (2) Staff Engagement: A series of staff engagement events were conducted including Staff Forum, IPMOE Hospital Visit, Kick-off Ceremony and establishment of IPMOE Webpage for familiarizing the forthcoming implementation with frontline staff. (3) Well-organized training program: from Workshop to Workplace Two different IPMOE training programs were tailor-made which aimed at introducing the core features of administration module. Fifty-five identical training classes and six train-the-trainer workshops were organized at 2-3Q 2015. Lending Scheme on IPMOE hardware for hands-on practicing was launched and further extended the training from workshop to workplace. (4) Standard Guidelines and Workflow: the related workflow and guidelines are developed which facilitates users to acquire the competence towards IPMOE and fully familiarize with the standardized contingency plan. (5) Facilities and Equipment: The installations of IPMOE hardware were promptly arranged for rollout. Besides, IPMOE training venue was well-established for staff training. (6) Risk Management Strategy: UCH Medication Safety Forum is organized in December 2015 for sharing “Tricks & Tips” on IPMOE which further disseminate at webpage for arousal of medication safety. Hospital-wide annual audit on drug administration was planned to figure out the compliance and deliberate the rooms for improvement. Results: Through the comprehensive training plan, over 1,000 UCH nurses attended the training program with positive feedback. They agreed that their competence on using IPMOE was enhanced. By the end of November 2015, 28 wards (over 1,000 Inpatient-bed) involving departments of M&G, SUR, O&T and O&G have been successfully rolled out IPMOE in 5-month. A smooth and safe transition of implementation of IPMOE was achieved. Eventually, we all get prepared for embedding IPMOE into daily nursing and work altogether for medication safety at UCH.

Keywords: drug administration, inpatient medication order entry system, medication safety, nursing informatics

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1603 An Extended Inverse Pareto Distribution, with Applications

Authors: Abdel Hadi Ebraheim

Abstract:

This paper introduces a new extension of the Inverse Pareto distribution in the framework of Marshal-Olkin (1997) family of distributions. This model is capable of modeling various shapes of aging and failure data. The statistical properties of the new model are discussed. Several methods are used to estimate the parameters involved. Explicit expressions are derived for different types of moments of value in reliability analysis are obtained. Besides, the order statistics of samples from the new proposed model have been studied. Finally, the usefulness of the new model for modeling reliability data is illustrated using two real data sets with simulation study.

Keywords: pareto distribution, marshal-Olkin, reliability, hazard functions, moments, estimation

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1602 Identifying Model to Predict Deterioration of Water Mains Using Robust Analysis

Authors: Go Bong Choi, Shin Je Lee, Sung Jin Yoo, Gibaek Lee, Jong Min Lee

Abstract:

In South Korea, it is difficult to obtain data for statistical pipe assessment. In this paper, to address these issues, we find that various statistical model presented before is how data mixed with noise and are whether apply in South Korea. Three major type of model is studied and if data is presented in the paper, we add noise to data, which affects how model response changes. Moreover, we generate data from model in paper and analyse effect of noise. From this we can find robustness and applicability in Korea of each model.

Keywords: proportional hazard model, survival model, water main deterioration, ecological sciences

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1601 Role of Vitamin-D in Reducing Need for Supplemental Oxygen Among COVID-19 Patients

Authors: Anita Bajpai, Sarah Duan, Ashlee Erskine, Shehzein Khan, Raymond Kramer

Abstract:

Introduction: This research focuses on exploring the beneficial effects if any, of Vitamin-D in reducing the need for supplemental oxygen among hospitalized COVID-19 patients. Two questions are investigated – Q1)Doeshaving a healthy level of baselineVitamin-D 25-OH (≥ 30ng/ml) help,andQ2) does administering Vitamin-D therapy after-the-factduring inpatient hospitalization help? Methods/Study Design: This is a comprehensive, retrospective, observational study of all inpatients at RUHS from March through December 2020 who tested positive for COVID-19 based on real-time reverse transcriptase–polymerase chain reaction assay of nasal and pharyngeal swabs and rapid assay antigen test. To address Q1, we looked atall N1=182 patients whose baseline plasma Vitamin-D 25-OH was known and who needed supplemental oxygen. Of this, a total of 121 patients had a healthy Vitamin-D level of ≥30 ng/mlwhile the remaining 61 patients had low or borderline (≤ 29.9ng/ml)level. Similarly, for Q2, we looked at a total of N2=893 patients who were given supplemental oxygen, of which713 were not given Vitamin-D and 180 were given Vitamin-D therapy. The numerical value of the maximum amount of oxygen flow rate(dependent variable) administered was recorded for each patient. The mean values and associated standard deviations for each group were calculated. Thesetwo sets of independent data served as the basis for independent, two-sample t-Test statistical analysis. To be accommodative of any reasonable benefitof Vitamin-D, ap-value of 0.10(α< 10%) was set as the cutoff point for statistical significance. Results: Given the large sample sizes, the calculated statistical power for both our studies exceeded the customary norm of 80% or better (β< 0.2). For Q1, the mean value for maximumoxygen flow rate for the group with healthybaseline level of Vitamin-D was 8.6 L/min vs.12.6L/min for those with low or borderline levels, yielding a p-value of 0.07 (p < 0.10) with the conclusion that those with a healthy level of baseline Vitamin-D needed statistically significant lower levels of supplemental oxygen. ForQ2, the mean value for a maximum oxygen flow rate for those not administered Vitamin-Dwas 12.5 L/min vs.12.8L/min for those given Vitamin-D, yielding a p-valueof 0.87 (p > 0.10). We thereforeconcludedthat there was no statistically significant difference in the use of oxygen therapy between those who were or were not administered Vitamin-D after-the-fact in the hospital. Discussion/Conclusion: We found that patients who had healthy levels of Vitamin-D at baseline needed statistically significant lower levels of supplemental oxygen. Vitamin-D is well documented, including in a recent article in the Lancet, for its anti-inflammatory role as an adjuvant in the regulation of cytokines and immune cells. Interestingly, we found no statistically significant advantage for giving Vitamin-D to hospitalized patients. It may be a case of “too little too late”. A randomized clinical trial reported in JAMA also did not find any reduction in hospital stay of patients given Vitamin-D. Such conclusions come with a caveat that any delayed marginal benefits may not have materialized promptly in the presence of a significant inflammatory condition. Since Vitamin-D is a low-cost, low-risk option, it may still be useful on an inpatient basis until more definitive findings are established.

Keywords: COVID-19, vitamin-D, supplemental oxygen, vitamin-D in primary care

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1600 Identifying Diabetic Retinopathy Complication by Predictive Techniques in Indian Type 2 Diabetes Mellitus Patients

Authors: Faiz N. K. Yusufi, Aquil Ahmed, Jamal Ahmad

Abstract:

Predicting the risk of diabetic retinopathy (DR) in Indian type 2 diabetes patients is immensely necessary. India, being the second largest country after China in terms of a number of diabetic patients, to the best of our knowledge not a single risk score for complications has ever been investigated. Diabetic retinopathy is a serious complication and is the topmost reason for visual impairment across countries. Any type or form of DR has been taken as the event of interest, be it mild, back, grade I, II, III, and IV DR. A sample was determined and randomly collected from the Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N.M.C., A.M.U., Aligarh, India. Collected variables include patients data such as sex, age, height, weight, body mass index (BMI), blood sugar fasting (BSF), post prandial sugar (PP), glycosylated haemoglobin (HbA1c), diastolic blood pressure (DBP), systolic blood pressure (SBP), smoking, alcohol habits, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), physical activity, duration of diabetes, diet control, history of antihypertensive drug treatment, family history of diabetes, waist circumference, hip circumference, medications, central obesity and history of DR. Cox proportional hazard regression is used to design risk scores for the prediction of retinopathy. Model calibration and discrimination are assessed from Hosmer Lemeshow and area under receiver operating characteristic curve (ROC). Overfitting and underfitting of the model are checked by applying regularization techniques and best method is selected between ridge, lasso and elastic net regression. Optimal cut off point is chosen by Youden’s index. Five-year probability of DR is predicted by both survival function, and Markov chain two state model and the better technique is concluded. The risk scores developed can be applied by doctors and patients themselves for self evaluation. Furthermore, the five-year probabilities can be applied as well to forecast and maintain the condition of patients. This provides immense benefit in real application of DR prediction in T2DM.

Keywords: Cox proportional hazard regression, diabetic retinopathy, ROC curve, type 2 diabetes mellitus

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1599 The Changing Landscape of Fire Safety in Covered Car Parks with the Arrival of Electric Vehicles

Authors: Matt Stallwood, Michael Spearpoint

Abstract:

In 2020, the UK government announced that sales of new petrol and diesel cars would end in 2030, and battery-powered cars made up 1 in 8 new cars sold in 2021 – more than the total from the previous five years. The guidance across the UK for the fire safety design of covered car parks is changing in response to the projected rapid growth in electric vehicle (EV) use. This paper discusses the current knowledge on the fire safety concerns posed by EVs, in particular those powered by lithium-ion batteries, when considering the likelihood of vehicle ignition, fire severity and spread of fire to other vehicles. The paper builds on previous work that has investigated the frequency of fires starting in cars powered by internal combustion engines (ICE), the hazard posed by such fires in covered car parks and the potential for neighboring vehicles to become involved in an incident. Historical data has been used to determine the ignition frequency of ICE car fires, whereas such data is scarce when it comes to EV fires. Should a fire occur, then the fire development has conventionally been assessed to match a ‘medium’ growth rate and to have a 95th percentile peak heat release of 9 MW. The paper examines recent literature in which researchers have measured the burning characteristics of EVs to assess whether these values need to be changed. These findings are used to assess the risk posed by EVs when compared to ICE vehicles. The paper examines what new design guidance is being issued by various organizations across the UK, such as fire and rescue services, insurers, local government bodies and regulators and discusses the impact these are having on the arrangement of parking bays, particularly in residential and mixed-use buildings. For example, the paper illustrates how updated guidance published by the Fire Protection Association (FPA) on the installation of sprinkler systems has increased the hazard classification of parking buildings that can have a considerable impact on the feasibility of a building to meet all its design intents when specifying water supply tanks. Another guidance on the provision of smoke ventilation systems and structural fire resistance is also presented. The paper points to where further research is needed on the fire safety risks posed by EVs in covered car parks. This will ensure that any guidance is commensurate with the need to provide an adequate level of life and property safety in the built environment.

Keywords: covered car parks, electric vehicles, fire safety, risk

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1598 An Impairment of Spatiotemporal Gait Adaptation in Huntington's Disease when Navigating around Obstacles

Authors: Naznine Anwar, Kim Cornish, Izelle Labuschagne, Nellie Georgiou-Karistianis

Abstract:

Falls and subsequent injuries are common features in symptomatic Huntington’s disease (symp-HD) individuals. As part of daily walking, navigating around obstacles may incur a greater risk of falls in symp-HD. We designed obstacle-crossing experiment to examine adaptive gait dynamics and to identify underlying spatiotemporal gait characteristics that could increase the risk of falling in symp-HD. This experiment involved navigating around one or two ground-based obstacles under two conditions (walking while navigating around one obstacle, and walking while navigating around two obstacles). A total of 32 participants were included, 16 symp-HD and 16 healthy controls with age and sex matched. We used a GAITRite electronic walkway to examine the spatiotemporal gait characteristics and inter-trail gait variability when participants walked at their preferable speed. A minimum of six trials were completed which were performed for baseline free walk and also for each and every condition during navigating around the obstacles. For analysis, we separated all walking steps into three phases as approach steps, navigating steps and recovery steps. The mean and inter-trail variability (within participant standard deviation) for each step gait variable was calculated across the six trails. We found symp-HD individuals significantly decreased their gait velocity and step length and increased step duration variability during the navigating steps and recovery steps compared with approach steps. In contrast, HC individuals showed less difference in gait velocity, step time and step length variability from baseline in both respective conditions as well as all three approaches. These findings indicate that increasing spatiotemporal gait variability may be a possible compensatory strategy that is adopted by symp-HD individuals to effectively navigate obstacles during walking. Such findings may offer benefit to clinicians in the development of strategies for HD individuals to improve functional outcomes in the home and hospital based rehabilitation program.

Keywords: Huntington’s disease, gait variables, navigating around obstacle, basal ganglia dysfunction

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1597 Treatment of Non-Small Cell Lung Cancer (NSCLC) With Activating Mutations Considering ctDNA Fluctuations

Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

Abstract:

Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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